Plant lectins are widely used to study changes in cell membrane fluidity induced by chemical carcinogens and viruses, disrupt tumorous cell membrane functions in vivo, promote intracellular biological responses and cell division, and agglutinate cells and blood group substances. Cell recognition by lectins is thought to involve surface glycoproteins and is often metal ion dependent. The most highly characterized lectin, Concanavalin A, normally requires the presence of divalent transition metal and calcium ions before its sugar binding site is created. This lectin binds to erythrocyte cell surfaces with hyperbolic saturation behavior and this process is strongly inhibited by monosaccharides which have a high affinity for the free protein. However, Con A shows positive cooperativity in binding to several other cell types including those which undergo cell division as a result of binding to surface receptors. Con A derivatives which are monovalent with respect to saccharide binding also show similar positive cooperativity in binding to lymphocytes and this suggests that the protein may recognize and bind to other non-saccharide surface receptor molecules. A number of Con A derivatives containing 90% enriched 13C nuclei distributed throughout the protein tertiary structure will be examined by magnetic resonance techniques free in solution and bound to cell surfaces. A specific lanthanide chelate site will be created in the protein and used to help assign each individual 13C resonance to a specific amino acid in the protein structure. These dynamic nuclear probes will provide direct evidence for the mode of Con A binding to cell membranes and thereby help establish a general mechanistic model of lectin action.